The goal of this project is to determine whether tumor promotion by phorbol esters, (TPA) proceeds via the release of arachidonic acid (AA) and the subsequent synthesis of prostaglandins (PG's) and hydroxy fatty acid (HFA). We have chosen the mouse embryo fibroblast (10T 1/2) as a model system. TPA caused a dose-dependent release of arachidonic acid and subsequent conversion to PG-HFA's. The major arachidonic acid metabolite produced by the TPA addition to cells was an unidentified HFA. Reported inhibitors of the various metabolic pathways of AA metabolism were studied with respect to potency and selectivity. Several inhibitors were selected and are now currently being studied for effects on TPA-induced cell transformation. We intend, hopefully, to correlate effects on promotion with effects on AA metabolism.